WO1991008452A1 - Dispositif a cristaux liquides destine a l'etalonnage et a l'essai d'instruments optiques - Google Patents
Dispositif a cristaux liquides destine a l'etalonnage et a l'essai d'instruments optiques Download PDFInfo
- Publication number
- WO1991008452A1 WO1991008452A1 PCT/US1990/006968 US9006968W WO9108452A1 WO 1991008452 A1 WO1991008452 A1 WO 1991008452A1 US 9006968 W US9006968 W US 9006968W WO 9108452 A1 WO9108452 A1 WO 9108452A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- optical
- shutter
- optical characteristics
- instrument
- set forth
- Prior art date
Links
- 230000003287 optical effect Effects 0.000 title claims abstract description 106
- 238000012360 testing method Methods 0.000 title description 17
- 239000004973 liquid crystal related substance Substances 0.000 title description 16
- 238000000034 method Methods 0.000 claims abstract description 11
- 230000005540 biological transmission Effects 0.000 claims description 16
- 230000004044 response Effects 0.000 claims description 12
- 210000002381 plasma Anatomy 0.000 claims description 6
- 230000008859 change Effects 0.000 claims description 4
- 206010053567 Coagulopathies Diseases 0.000 claims description 2
- 230000035602 clotting Effects 0.000 claims description 2
- 238000007493 shaping process Methods 0.000 claims 1
- 238000002834 transmittance Methods 0.000 description 12
- 238000004088 simulation Methods 0.000 description 11
- 230000015271 coagulation Effects 0.000 description 9
- 238000005345 coagulation Methods 0.000 description 9
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 230000001143 conditioned effect Effects 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 238000010586 diagram Methods 0.000 description 4
- 238000011156 evaluation Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 239000004988 Nematic liquid crystal Substances 0.000 description 3
- 101100536354 Drosophila melanogaster tant gene Proteins 0.000 description 2
- 230000023555 blood coagulation Effects 0.000 description 2
- 239000000919 ceramic Substances 0.000 description 2
- 230000003750 conditioning effect Effects 0.000 description 2
- 238000013041 optical simulation Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 239000004593 Epoxy Substances 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- AMGQUBHHOARCQH-UHFFFAOYSA-N indium;oxotin Chemical compound [In].[Sn]=O AMGQUBHHOARCQH-UHFFFAOYSA-N 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
- G01J1/00—Photometry, e.g. photographic exposure meter
- G01J1/02—Details
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/27—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands using photo-electric detection ; circuits for computing concentration
- G01N21/274—Calibration, base line adjustment, drift correction
- G01N21/278—Constitution of standards
Definitions
- the present invention relates to a device for optical calibration of an optical instrument that measures optical characteristics, such as turbidity of a sample, and more specifically to a to device for simulating changes in light transmission and/or. scattering to provide a simulated operating environment for the optical instrument.
- Instruments which analyze material based upon measure ⁇ ment of changes in optical properties of the material reguire both initial and periodic calibration and testing.
- a standard or reference reagent is necessary in order to adjust the instrument to provide a reading which represents a reference point.
- Procedures for calibration include the use of standard reagents having known values for the properties to be analyzed through the evaluation of the resultant optical properties.
- currently employed procedures for the testing of blood coagulation instruments include the use of standard reagents and standard blood samples. There are a number of inherent uncertainties associated with both standard blood samples and standard reagent preparation and handling reguiring that a number of runs be performed in order to establish sufficient confidence in the results.
- a controllable shutter having electrically alterable optical charac ⁇ teristics is placed across the optical path of the instru ⁇ ment and a control mechanism is connected to the controll ⁇ able shutter for selectively providing a variable voltage to the shutter to electrically alter optical characteris- tics of the shutter in a controlled manner so that the optical characteristics of the shutter correspond to selected optical characteristics.
- the shutter is preferably shaped to fit into a sample receptacle of the optical instrument.
- Figure 1 is a perspective view showing a schematic representation of an optical instrument and controllable shutter according to an embodiment of the invention.
- Figure 2 is a cross-sectional view of a liquid crystal shutter according the present invention.
- Figure 3 is a logical flow diagram illustrating the test operation of the present invention.
- Figure 4 is a graph representing the optical response of the liquid crystal shutter of the present invention.
- Figure 5 is a graph illustrating the shutter transfer characteristics which illustrates the transmission characteristics of the shutter as a function of applied voltage.
- Figure 6 is a block circuit diagram showing the operational interaction of the shutter driver and the measuring instrument.
- a coagulation analysis device 12 having a light responsive sensor portion 14, which includes one or more light emitters and/or receivers (not shown) .
- a blood plasma sample is placed in a vial and liquid coagulation reagents are added.
- the vial is then placed in a slot 16 in sensor 14 and the blood allowed to coagulate.
- the plasma sample coagulates, light scattered by the plasma sample increases and the sample becomes less transmissive. This optical change is detected by a properly functioning sensor, the details of which are known and form no part of the present invention.
- the sensor In order to ensure that the sensor functions properly, it is necessary to test the sensor mechanism and to calibrate it if necessary.
- the sensor must detect with a degree of precision the time at which the sample crosses over the threshold of coagulation through detecting changes in its optical transmission. Therefore, it is necessary to provide the sensor with an optical stimulus which cor- responds to the optical change in a sample. This can be done by providing an actual blood plasma sample with coagulation reagents. If the sample adequately represents the "average person's" plasma, then the measured coagula ⁇ tion time should approximate the statistical mean of coagulation times for the general population.
- an optical stimulus simulating coagulation is provided by an optical element or shutter 18, which can be electrically controlled to exhibit optical characteristics which simulate changes in optical transmission of a standardized sample.
- Shutter 18 includes a liquid crystal having optical transmission characteristics which can be varied through the application of a selectively variable electrical voltage as will be described in greater detail below.
- a controller 36 which can be a computer or similar operator interface mechanism, or an automated piece of hardware, sends a digital signal to a D/A converter and shutter driver 38, which supplies a corresponding voltage to the shutter 18. Controller 36 can be made to generate and send signals to simulate the desired optical charac ⁇ teristic. Typically a variety of simulations can be selected by the operator through controller 36. As the simulation is run, the controller 36 receives data from instrument 12 indicative of the instrument's standard analysis of the optical characteristics of the simulation. These data are collected by controller 36 or by a separate instrument as desired.
- the shutter comprises a liquid crystal layer 32 sandwiched between transparent electrode layers 28 and 30 of indium tin oxide (a ceramic semiconduc ⁇ tor comprised of 1 ⁇ 03 and Sn ⁇ 2) , which are in turn covered by transparent.
- Terminals 20 and 22 form an electrical contact with electrode layers 28 and 30.
- Terminals 20 and 22 are connected to electrodes 28 and 30 by a silver epoxy 34 to prevent damage of the ceramic electrodes through heating and mechanical stress.
- the shutter assembly shown in Figure 2 may be enclosed in clear acrylic (not shown) , or other suitable material, to allow for repeated insertion into optical slots 16 without undue stress on the liquid crystal film and/or layers. This encasement also shields the film from exposure to moisture which can alter the performance characteristics of the film. It is important to isolate the film and electrode layers from mechanical stress and from moisture since repeated use is almost certain to subject the shutter to both.
- Liquid crystal layer 32 comprises a nematic liquid crystal as disclosed, for example, in U.S. Patent No.
- the liquid crystal film exhibits the spectral transmissive characteristics listed in tables I and II when powered by a square wave signal at 1 KHz of 10 volts and 0 volts, respectively:
- the dynamic range of variable transmission allows for a considerable degree of controlled optical simulation. This range, combined with the linearity of response which can be achieved if shutter 18 is properly driven, allows shutter 18 to be used for testing a variety of optical instruments that detect changes in light transmission in accordance with the principles of the invention.
- the liquid crystal film utilized exhibits an optical response which is, by itself, not linear as a function of voltage amplitude. Therefore, in order to generate a reasonable simulation of the light transmission characteristics of the test sample being simulated, it is necessary to create a proportional voltage simulation characteristic. As illustrated in Figure 5, there is a non-linear relationship between the voltage applied to the liquid crystal and its optical response characteristics.
- the appropriate characteristic for the electrical drive signal applied to shutter 18 is derived through conditioning of the characteristic exhibited by the optical signal to be simulated. The conditioning comprises taking the characteristic of the desired optical signal to be simulated, such as Signal A, illustrated in Figure 4, and through use of a mathematical algorithm arriving at an electrical signal characteristic for driving the liquid crystal to generate the desired simulated optical charac ⁇ teristic
- the original waveform A is col ⁇ lected from the optical turbidity instrument 12 during a run of the instrument under standardized conditions.
- the waveform A must then be conditioned so that the electrical signal based on the conditioned waveform will drive the shutter 18 to produce characteristic B.
- Figure 5 illustrates the transmittance to voltage relationship for the shutter material. This curve is determined by placing a shutter 18 in the optical path of the sensor portion 14 of the analysis device 12, and then feeding a known voltage into the shutter 18 and correlating the detected transmittance. The known voltage is varied to determine the relationship across a voltage and transmit ⁇ tance range. The relationship between voltage and resul- tant transmittance is utilized in calculating a variable voltage drive signal to replicate the optical characteris ⁇ tic A.
- V 25600 ⁇ A tan (Bx-C) +D+Ex+Fx 2 +Gx 3 +Hx 4 +Ix 5 ⁇
- V voltage of drive signal
- Distinct curves such as characteristic A, can be collected for any number or variety of optical transmit ⁇ tance situations.
- the curves can be conditioned so that they can be simulated by driving shutter 18 with a voltage signal taking into account the voltage to transmittance ratio derived above.
- the technique for learning and replicating the optical transmittance of a given event can thus be summarized as follows. First the event is performed, measured and repeated several times. Each of the measured transmittance characteristics is recorded, and they are collected together and evaluated to determine a standard transmit ⁇ tance curve. Once the standard transmittance curve is derived, an electrical signal is arrived at which will produce a replication of that transmittance curve by electrically driving an electrically controllable shutter. The value of the points along the standard transmittance curve are conditioned or converted into appropriate voltage values for driving the shutter to replicate the transmit ⁇ tance value points along the transmittance curve, as described above. It will be appreciated by those skilled in the art that any desired waveform (e.g.
- a square wave may be conditioned in the above manner and used for calibration in accordance with the principles of the invention.
- the shutter is then driven with the voltage signal to replicate the standardized curve.
- the liquid crystal exhibits an imperfect amplitude response which is partly due to hysteresis of the liquid crystal. Therefore, it is desirable to utilize an overdrive algorithm in conjunction with the compensation algorithm to improve the simulation accuracy, in order to achieve the results illustrated by the characteristics in Figure 4.
- the overdrive algorithm computes a running average ahead of the data point being manipulated, and alters the data point according to a fraction of the difference between it and the running average.
- Figure 3 illustrates a logical flow diagram of the functional steps for simulation and evaluation of a test in the context of the system shown in Figure 1.
- the system is first initialized and then a selection menu is presented to the operator to establish the appropriate settings on optical instrument 12 and to select the simulation to be run.
- the appropriate files are loaded and the operator is instructed to begin the analysis.
- Controller 36 then sends appropriate data to shutter 18 for the selected simulation, as the instrument 12 performs the appropriate evaluation on the simulated transmission. Either the raw transmission data or only the final resultant clotting times are retrieved by the controller as selected by the operator.
- Controller 36 will then analyze the received data in either form and determine if the data are consistent with the expected results for the signals transmitted.
- the controller can be programmed to determine consistency within a given range in order to determine accuracy.
- controller 36 can be utilized to evaluate the noise level in the received data to determine operational characteristics of the instrument. Since the optical signal from shutter 18 is smooth, the data should demonstrate a smooth response. A noisy response can indicate a deficiency in optical sensor 14 or associated circuitry of instrument 12. This analysis cannot be reliably performed with reagent sample calibration, because a reproducible smooth optical input cannot be assured. It has been determined that for the purposes of optical testing the film is optimally driven by a square wave at a frequency of 1 KHz. At low driving frequencies the optical transmission characteristics are modulated and above 1 KHz the film can be damaged. It is also necessary to drive the film with a net zero DC waveform to avoid an electrical potential imbalance which will also damage the film.
- Figure 6 illustrates a block diagram of the control circuitry for driving the shutter and for receiving the data from the optical instrument in greater detail.
- the circuitry is comprised of three sections, the controller or computer 36, a data acquisition circuit 40 and a custom driver circuit 42.
- Data acquisition circuit 40 and custom driver circuit 42 comprise the generalized block 38 referred to as the D/A converter and driver of Figure 1.
- Data acquisition circuit 40 provides the appropriate timing for controlling the simulation rate. Circuit 40 also converts the digital signal from controller 36 to an analog voltage for driver circuit 42.
- Driver circuit 42 includes a power supply 44, low power converter 46, a variable voltage regulator 48, a square wave oscillator 50 and an output driver 52. The circuit provides the neces ⁇ sary controlled voltage to drive shutter 18 as described hereinabove.
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- Physics & Mathematics (AREA)
- Spectroscopy & Molecular Physics (AREA)
- General Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Mathematical Physics (AREA)
- Biochemistry (AREA)
- Theoretical Computer Science (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Investigating Or Analysing Materials By Optical Means (AREA)
- Liquid Crystal (AREA)
- Testing Of Optical Devices Or Fibers (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Reciprocating Pumps (AREA)
Abstract
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE69021392T DE69021392T2 (de) | 1989-11-29 | 1990-11-29 | Flüssigkristallvorrichtung zum kalibrieren und testen optischer instrumente. |
KR1019920701250A KR0151703B1 (ko) | 1989-11-29 | 1990-11-29 | 광학 계기의 교정 및 테스팅용 액정장치 |
EP91900473A EP0502952B1 (fr) | 1989-11-29 | 1990-11-29 | Dispositif a cristaux liquides destine a l'etalonnage et a l'essai d'instruments optiques |
FI922200A FI102213B (fi) | 1989-11-29 | 1992-05-14 | Nestekidelaite optisten instrumenttien kalibrointiin ja testaukseen |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US07/442,604 US5030005A (en) | 1989-11-29 | 1989-11-29 | Liquid crystal device for calibration and testing of optical instruments |
US442,604 | 1989-11-29 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1991008452A1 true WO1991008452A1 (fr) | 1991-06-13 |
Family
ID=23757436
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1990/006968 WO1991008452A1 (fr) | 1989-11-29 | 1990-11-29 | Dispositif a cristaux liquides destine a l'etalonnage et a l'essai d'instruments optiques |
Country Status (14)
Country | Link |
---|---|
US (1) | US5030005A (fr) |
EP (1) | EP0502952B1 (fr) |
JP (1) | JPH05503151A (fr) |
KR (1) | KR0151703B1 (fr) |
AT (1) | ATE125939T1 (fr) |
AU (1) | AU634619B2 (fr) |
CA (1) | CA2072742A1 (fr) |
DE (1) | DE69021392T2 (fr) |
DK (1) | DK0502952T3 (fr) |
ES (1) | ES2077839T3 (fr) |
FI (1) | FI102213B (fr) |
IE (1) | IE67655B1 (fr) |
WO (1) | WO1991008452A1 (fr) |
ZA (1) | ZA909530B (fr) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2248925B (en) * | 1990-09-18 | 1994-08-24 | Anthony Michael Charles Davies | Method and apparatus for calibrating a spectrometer |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5416575A (en) * | 1991-11-18 | 1995-05-16 | Schwartz; Mark | Method and system for calibrating an optical density measurement apparatus |
EP0562424B1 (fr) * | 1992-03-25 | 1997-05-28 | Texas Instruments Incorporated | Systéme integré d'étalonnage optique |
US5369484A (en) * | 1992-11-09 | 1994-11-29 | Akzo N.V. | Multiple discrete analyzer test apparatus and method |
DE19531556A1 (de) * | 1995-08-28 | 1997-03-06 | Cafer Borucu | Phasenschieber |
US6061128A (en) * | 1997-09-04 | 2000-05-09 | Avocet Medical, Inc. | Verification device for optical clinical assay systems |
US7576853B2 (en) * | 2005-06-10 | 2009-08-18 | The Research Foundation Of State University Of New York | Electronically modulated dynamic optical phantoms for biomedical imaging |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4435047A (en) * | 1981-09-16 | 1984-03-06 | Manchester R & D Partnership | Encapsulated liquid crystal and method |
US4595292A (en) * | 1983-07-29 | 1986-06-17 | The Perkin-Elmer Corporation | Apparatus for detecting coherent radiation and unequal path interferometers |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4435006A (en) * | 1980-05-12 | 1984-03-06 | Kabushiki Kaisha Yamamoto Suiatsu Kogyosho | Automatic pressurized connecting device |
DE3203800A1 (de) * | 1982-02-04 | 1983-08-11 | Jos. Schneider, Optische Werke, AG, 6550 Bad Kreuznach | Beleuchtungseinrichtung eines testprojektors fuer farbfernsehkameras |
US4556289A (en) * | 1983-03-21 | 1985-12-03 | Manchester R & D Partnership | Low birefringence encapsulated liquid crystal and optical shutter using same |
US4756884A (en) * | 1985-08-05 | 1988-07-12 | Biotrack, Inc. | Capillary flow device |
-
1989
- 1989-11-29 US US07/442,604 patent/US5030005A/en not_active Expired - Fee Related
-
1990
- 1990-11-22 IE IE422990A patent/IE67655B1/en not_active IP Right Cessation
- 1990-11-27 ZA ZA909530A patent/ZA909530B/xx unknown
- 1990-11-29 CA CA002072742A patent/CA2072742A1/fr not_active Abandoned
- 1990-11-29 DK DK91900473.9T patent/DK0502952T3/da active
- 1990-11-29 KR KR1019920701250A patent/KR0151703B1/ko not_active IP Right Cessation
- 1990-11-29 JP JP3501110A patent/JPH05503151A/ja active Pending
- 1990-11-29 AT AT91900473T patent/ATE125939T1/de not_active IP Right Cessation
- 1990-11-29 EP EP91900473A patent/EP0502952B1/fr not_active Expired - Lifetime
- 1990-11-29 DE DE69021392T patent/DE69021392T2/de not_active Expired - Fee Related
- 1990-11-29 ES ES91900473T patent/ES2077839T3/es not_active Expired - Lifetime
- 1990-11-29 AU AU69027/91A patent/AU634619B2/en not_active Ceased
- 1990-11-29 WO PCT/US1990/006968 patent/WO1991008452A1/fr active IP Right Grant
-
1992
- 1992-05-14 FI FI922200A patent/FI102213B/fi active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4435047A (en) * | 1981-09-16 | 1984-03-06 | Manchester R & D Partnership | Encapsulated liquid crystal and method |
US4595292A (en) * | 1983-07-29 | 1986-06-17 | The Perkin-Elmer Corporation | Apparatus for detecting coherent radiation and unequal path interferometers |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2248925B (en) * | 1990-09-18 | 1994-08-24 | Anthony Michael Charles Davies | Method and apparatus for calibrating a spectrometer |
Also Published As
Publication number | Publication date |
---|---|
ES2077839T3 (es) | 1995-12-01 |
FI102213B1 (fi) | 1998-10-30 |
AU6902791A (en) | 1991-06-26 |
IE67655B1 (en) | 1996-04-17 |
DE69021392T2 (de) | 1996-01-18 |
KR0151703B1 (ko) | 1998-12-01 |
US5030005A (en) | 1991-07-09 |
IE904229A1 (en) | 1991-06-05 |
KR920704106A (ko) | 1992-12-19 |
EP0502952B1 (fr) | 1995-08-02 |
DK0502952T3 (da) | 1995-09-25 |
EP0502952A4 (en) | 1993-03-24 |
FI922200A0 (fi) | 1992-05-14 |
AU634619B2 (en) | 1993-02-25 |
FI922200A (fi) | 1992-05-14 |
EP0502952A1 (fr) | 1992-09-16 |
DE69021392D1 (de) | 1995-09-07 |
ATE125939T1 (de) | 1995-08-15 |
FI102213B (fi) | 1998-10-30 |
ZA909530B (en) | 1991-11-27 |
JPH05503151A (ja) | 1993-05-27 |
CA2072742A1 (fr) | 1991-05-30 |
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